Diagnostic and prognostic impact of serum‐soluble UL 16‐binding protein 2 in lung cancer patients

UL 16‐binding protein 2 ( ULBP 2) is one of the ligands for NKG2D ( NKG2DL ). ULBP 2 expression is induced in transformed cells and is recognized by immune effector cells via the activating NKG2D immunoreceptor. Soluble forms of NKG2DL have been reported in the serum of patients with several types of cancer. The present study investigated the diagnostic and prognostic significance of serum‐soluble ULBP 2 (s ULBP 2) in lung cancer patients. We used flow cytometry to evaluate the surface expression of NKG2DL by various lung cancer cells, while s ULBP 2 was measured using our original ELISA . In addition, the immunological effect of s ULBP 2 on peripheral blood mononuclear cells ( PBMC ) was examined by the 51 C r release assay. We found that ULBP 2 was highly expressed and that the s ULBP 2 level was elevated in supernatants of cultured non‐small‐cell lung cancer ( NSCLC ) cells as well as in the serum of NSCLC patients. ULBP 2 levels were especially high in squamous cell carcinoma ( SQ ) patients. Clinical stage III B and IV NSCLC patients with a s ULBP 2 level ≥8.7 pg/mL showed significantly shorter survival than patients with s ULBP 2 <8.7 pg/mL. In multivariate analysis, a s ULBP 2 level ≥8.7 pg/mL (hazard ratio [ HR ], 2.13; P  = 0.038) and clinical stage IV ( HR , 2.65; P  = 0.019) were independent determinants of a poor outcome. As a possible mechanism, we demonstrated that s ULBP 2 directly suppresses the cytolytic activity of PBMC . In conclusion, ULBP 2 is the most significant NKG2DL for lung cancer, and s ULBP 2 is useful in the diagnosis of SQ and as a prognostic indicator for patients with advanced NSCLC . ( Cancer Sci , doi: 10.1111/j.1349‐7006.2012.02330.x, 2012)